CIDRI-Africa jump-starts six COVID-19 research projects

The University of Cape Town’s (UCT) Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) has awarded “pump-priming” funding for six COVID-19 research projects.

CIDRI-Africa is pleased to have awarded “pump-priming” funding for six COVID-19 research projects. COVID-19 is the disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the 2^nd of August 2020, 511 485 COVID-19 cases and 8366 related deaths had been recorded in South Africa.

There are grave concerns about the impact that COVID-19 might have in South Africa owing to considerable existing epidemics like HIV and TB, which may increase vulnerability to and severity of COVID-19 infection. It is therefore very important to support locally relevant, locally conducted COVID-19 research that will answer questions about the disease in our population.

This internal CIDRI-Africa funding scheme has provided catalytic, short-term support which the awardees will use to rapidly initiate research programmes. The projects funded cover a range of COVID-19 related topics from treatment trials to diagnostics to serological analyses and answer several critical questions about the virus, the disease, and the pandemic.

What happens if you have already been exposed to a different coronavirus?

Wendy Burgers will be characterising cross-reactive and durable immunity to SARS-CoV-2; in collaboration with Ntobeko Ntusi from the Dept of Medicine, she and her team will work with a cohort of South African healthcare workers from whom blood samples are being collected. The incidence of SARS-CoV-2 among healthcare workers is currently unknown, but it is estimated that up to 30% may become infected with SARS-CoV-2, and the team will follow the cohort before, during and after illness. By following the cohort of participants over the next 2 years, Wendy’s team will generate information on baseline pre-existing immune responses (to circulating ‘common cold’ coronaviruses) in uninfected individuals as well as memory responses that develop after recovery from COVID-19. The aim of this research is to determine whether these pre-existing responses (either T cell or antibody responses) influence clinical outcome and immune memory. Her team will also develop tools to define detailed immunological responses to SARS-CoV-2, and have already established and validated an in-house ELISA to characterise antibody responses to SARS-CoV-2 Spike protein.

How does COVID-19 affect children?

Both Heather Zar and Liesl Zülkhe will be investigating various aspects of COVID-19 infection in children. Heather, who leads the Drakenstein Child Health Study, an established birth cohort study in Paarl, will prospectively investigate the epidemiology of, risk factors for and serological responses to COVID-19 in children. As in Wendy’s cohort, Heather’s cohort data includes information about documented previous infection with endemic coronaviruses and the antibody responses they result in, to evaluate possible cross protection against COVID-19.  All 900 children in the Drakenstein cohort will be followed and evaluated for SARS-CoV-2 infection or disease, with ongoing collection of risk factors including environmental, nutritional, sociodemographic, maternal health, infectious exposures, and underlying illness. A key COVID-19 knowledge gap is why children develop predominantly asymptomatic infection or mild disease; Heather’s study will help to fill this gap by investigating the possible role of endemic coronaviruses in COVID-19 protection, and will also characterise the disease spectrum and determinants in children. The results will be valuable in informing possible protective mechanisms against COVID and help to inform vaccine strategies and markers of immunity.

Liesl Zülkhe will be investigating the incidence of post-inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS). PIMS-TS has shown a concerning bias towards children of black, Asian and minority ethnic (BAME) communities in other countries and there is an emerging cluster of children critically ill with PIMS-TS in the Western Cape. Liesl’s project aims to understand the atypical immune response that may result in PIMS-TS in this cluster of children. Her research will also capture data from children with COVID-19 and PIMS-TS across South Africa and create a collaborative platform to collect these data from across sub-Saharan Africa. These data will provide an in-depth understanding of SARS-CoV-2 and PIMS-TS in children in sub-Saharan Africa, providing valuable data for locally appropriate, evidence-based disease mitigation, risk stratification and treatment strategies.

What is the ideal biological specimen for detecting infection with SARS-CoV-2?

Nasopharyngeal swabs are the current standard, but collection of these specimens requires close contact between healthcare workers and patients, which poses a risk of viral transmission. Helen Cox will be examining whether self-collected saliva is a viable specimen for detection of SARS-CoV-2 in adults by comparing the detection rate in paired saliva, mid-turbinate (nasal), and nasopharyngeal samples. Collection of saliva may substantially decrease the risk of transmission of SARS-CoV-2 from patients to healthcare workers; the collection process is non-invasive and may prove transformative for patient diagnostics and surveillance. In addition, knowledge of differences in the mean PCR cycle threshold values of positive paired swabs stratified by symptom duration may guide policy as to when saliva versus nasal swabs versus nasopharyngeal swabs may be the preferred diagnostic source. Altogether, Helen’s research could further reduce the risk to healthcare workers, decrease personal protection equipment usage, and reduce visits to overburdened health-care facilities. 

How can we treat mild COVID-19 in out-patients?

Sean Wasserman will be contributing answers to this broad question in his trial of favipiravir versus placebo for treatment of mild COVID-19 in outpatients in South Africa. While remdesivir and dexamethasone have shown benefit in hospitalised patients with severe COVID-19, there are still no proven efficacious and safe interventions for patients with mild disease. Identifying interventions that reduce duration of illness and COVID-19 hospitalisations is a public health priority. Participants eligible for Sean’s trial will be randomly assigned to receive favipiravir or placebo for seven days and will be followed up to assess whether they have had to be hospitalised for COVID-19. Favipiravir is a promising agent for use in African settings for several reasons: it is orally administered, well-tolerated with minimal safety monitoring requirements, and is not expected to have significant drug-drug interactions with antiretrovirals or TB treatment.

Remdesivir and dexamethasone might help severe COVID-19 cases, but what else can be done?

Sean (with Robert J Wilkinson) will also conduct a clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19 (PROTECT-Patient Trial). COVID-19 convalescent plasma&nsp;(CCP) is plasma—the colourless part of blood that does not contain red blood cells—collected from donors who have recovered from COVID-19 and have likely produced antibodies to SARS-CoV-2. Six hundred participants admitted to participating hospitals across South Africa will be randomized to receive either CCP or saline placebo control and assessed for clinical improvement at several time points up to 28 days after receiving the treatment. It is critical to find therapies that improve outcomes for hospitalised patients with severe COVID-19, but effective treatment options must be accessible and affordable for all South Africans; CCP is considered a potential treatment option that may fulfil these criteria.

These research projects will begin to provide answers and avenues for action to respond to the COVID-19 pandemic in South Africa and elsewhere. Our awardees will use these first rapid-access, pump-priming funds to initiate their research programmes and will apply for external funding from other bodies to progress their research further.